In vitro induction of adult hepatic progenitor cells into insulin-producing cells

In vitro induction of adult hepatic progenitor cells into insulin-producing cells
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DOI:
10.1016/j.bbrc.2004.04.059
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发表时间:
2004-06-04
影响因子:
3.1
通讯作者:
Shimizu, A
Shimizu, A
中科院分区:
生物学4区
文献类型:
--
作者:
Nakajima-Nagata, N;Sakurai, T;Shimizu, A

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器官特异性干细胞是组织再生中的天然祖细胞,具有在成体组织中分化为特化细胞的可塑性。在成人肝脏中鉴定的小肝细胞(SHC)就是这样一种细胞类型。在这里,我们表明,SHC,这是能够自我更新和分化为肝细胞,可以诱导产生胰岛素分泌细胞在适当的培养条件下。这些分化的细胞表达胰腺β细胞分化相关的转录本和肝细胞分化相关的转录本,如通过逆转录PCR/巢式PCR所示。此外,在这些细胞中同源域转录因子Pdx 1的强制表达有助于响应胰岛素促分泌素的胰岛素释放的增强。这些结果表明,这里描述的SHC具有分化成胰岛素分泌细胞的能力,并进一步支持工程化产生胰岛素分泌细胞可以为未来糖尿病治疗提供有用资源的想法。(C)2004年爱思唯尔公司All rights reserved.
Organ-specific stem cells are the natural progenitors in tissue regeneration and possess plasticity to differentiate into specialized cells in adult tissues. Small hepatocytes (SHCs) identified in the adult liver are one such cell type. Here we show that SHCs, which are capable of self-renewal and differentiation into hepatocytes, can be induced to generate insulin-producing cells under appropriate Culture conditions. These differentiated cells express pancreatic beta cell differentiation-related transcripts and hepatocyte differentiation-related transcripts, as shown by reverse-transcription PCR/nested PCR. In addition, enforced expression of the homeodomain transcription factor Pdx1 in these cells contributes to enhancement Of insulin release in response to insulin secretagogues. These results indicate that the SHCs described here have the ability to differentiate into insulin-producing cells, and further support the idea that engineering to generate insulin-secreting cells could provide a useful resource for future therapies for diabetes mellitus. (C) 2004 Elsevier Inc. All rights reserved.